Individual differences in Theory of Mind (ToM)-the ability to understand the mental states of others-are theorised to be predicted by socio-demographic and political factors. However, inconsistent ...findings on the relationships between various socio-demographic predictors and ToM, as well as a paucity of research on political predictors of ToM, have left a gap in the literature. Using a recently validated self-report measure of ToM in a large sample (N = 4202) we investigated the unique contributions of age, sex, socio-economic status, and political beliefs to ToM in adults. Except for age, all variables were correlated with ToM, but when accounting for the variance of other predictors in statistical analyses, political beliefs was no longer associated with ToM. Dominance analysis revealed that participant sex was the most important predictor of ToM. These findings help to address theoretical discrepancies in the existing literature and inform future methods and directions in social cognition research.
Prurigo nodularis (PN) is a chronic skin dermatosis with hyperkeratotic and intensely pruritic nodules. Managing PN‐associated itch is difficult because its aetiology is still unknown. This study ...aimed to investigate the correlation between itch intensity in PN and the expression of a pruritogenic cytokine interleukin (IL)‐31, its receptor complex components IL‐31 receptor α (IL‐31RA) and oncostatin M receptor β (OSMRβ), and oncostatin M (OSM), which is a ligand of OSMR β, through immunofluorescence staining examination. Itch intensity in PN was closely correlated with the number of dermal IL‐31(+) cells (Spearman's r = 0.551, p < 0.05), dermal IL‐31RA(+) cells (r = 0.475, p < 0.05) and dermal OSM(+) cells (r = 0.505, p < 0.05). In addition, the number of dermal OSMRβ (+) cells was increased in PN (t test, p < 0.05), despite not being correlated with itch intensity (Spearman's r = 0.375, p > 0.05). Major cellular sources of dermal IL‐31 were T cells (27.0% of total IL‐31–expressing cells) and macrophages (35.0%), while those of OSM were mainly T cells (49.8%) and mast cells (26.8%). IL‐31RA–expressing dermal cells were mostly mast cells (49.3%) and macrophages (36.6%), and OSMRβ was mainly expressed by macrophages (51.8%) in the dermis. These findings indicate that IL‐31 (mainly from macrophages and T cells) and OSM (principally from T cells and mast cells) stimulate dermal cells expressing IL‐31RA and OSMRβ (e.g. macrophages), which may further promote itch and inflammation in PN. This complex dermal milieu of cell/cytokine/receptor network can be a therapeutic target for PN‐associated itch.
Although immune activation is associated with HIV acquisition, the nature of inflammatory profiles that increase HIV risk, which may include responses to M. tuberculosis (Mtb) infection, are not well ...characterized.
We conducted a nested case-control study using cryopreserved samples from persons who did and did not acquire HIV during the multinational Step clinical trial of the MRKAd5 HIV-1 vaccine. PBMCs from the last HIV-negative sample from incident HIV cases and controls were stimulated with Mtb-specific antigens (ESAT-6/CFP-10) and analyzed by flow cytometry with intracellular cytokine staining and scored with COMPASS. We measured inflammatory profiles with five Correlates of TB Risk (CoR) transcriptomic signatures. Our primary analysis examined the association of latent Mtb infection (LTBI; IFNγ+CD4+ T cell frequency) or RISK6 CoR signature with HIV acquisition. Conditional logistic regression analyses, adjusted for known predictors of HIV acquisition, were employed to assess whether TB-associated immune markers were associated with HIV acquisition.
Among 465 participants, LTBI prevalence (21.5% controls vs 19.1% cases, p = 0.51) and the RISK6 signature were not higher in those who acquired HIV. In exploratory analyses, Mtb antigen-specific polyfunctional CD4+ T cell COMPASS scores (aOR 0.96, 95% CI 0.77, 1.20) were not higher in those who acquired HIV. Two CoR signatures, Sweeney3 (aOR 1.38 (1.07, 1.78) per SD change) and RESPONSE5 (0.78 (0.61, 0.98)), were associated with HIV acquisition. The transcriptomic pattern used to differentiate active vs latent TB (Sweeney3) was most strongly associated with acquiring HIV.
LTBI, Mtb polyfunctional antigen-specific CD4+ T cell activation, and RISK6 were not identified as risks for HIV acquisition. In exploratory transcriptomic analyses, two CoR signatures were associated with HIV risk after adjustment for known behavioral and clinical risk factors. We identified host gene expression signatures associated with HIV acquisition, but the observed effects are likely not mediated through Mtb infection.
Bacterial keratitis (bacterial infection of the cornea) is a major cause of vision loss worldwide. Given the rapid and aggressive nature of the disease, immediate broad-spectrum antibiotics are ...essential to adequately treat this disease. However, rising antibiotic resistance continues to accelerate, rendering many commonly used therapeutics increasingly ineffective. As such, there is a significant effort to understand the basic pathogenesis of common causative organisms implicated in keratitis in part, to fuel the development of novel therapies to treat this blinding disease. This review explores two common causes of bacterial keratitis,
Staphylococcus aureus
and
Pseudomonas aeruginosa
, with regards to the bacterial mediators of virulence as well as novel therapies on the horizon.
•Examined neural response to monetary and social reward in adolescents and parents.•Both types of reward elicited comparable striatal activation in youth and parents.•Striatal activation to monetary ...and social reward correlated in youth.•Striatal activation not correlated in youth-parent dyads for either type of reward.
Functional magnetic resonance imaging (fMRI) studies have indicated that the mesocorticolimbic dopamine system is heavily involved in all stages of reward processing. However, the majority of research has been conducted using monetary rewards and it is unclear to what extent other types of rewards, such as social rewards, evoke similar or different neural activation. There have also been few investigations into potential differences or similarities between reward processing in parents and offspring. The present study examined fMRI neural activation in response to monetary and social reward in a sample of 14–22-year-old adolescent girls (N = 145) and a biological parent (N = 124) and compared activation across adolescent-parent dyads (N = 82). Across all participants, both monetary and social reward elicited bilateral striatal activation, which did not differ between reward types or between adolescents and their parents. Neural activation in response to the different reward types were positively correlated in the striatum among adolescents and in the mPFC and OFC among parents. Overall, the present study suggests that both monetary and social reward elicit striatal activation regardless of age and provides evidence that neural mechanisms underlying reward processing may converge differentially among youth and adults.
Association of chromatin with lamin proteins at the nuclear periphery has emerged as a potential mechanism to coordinate cell type-specific gene expression and maintain cellular identity via gene ...silencing. Unlike many histone modifications and chromatin-associated proteins, lamina-associated domains (LADs) are mapped genome-wide in relatively few genetically normal human cell types, which limits our understanding of the role peripheral chromatin plays in development and disease.
To address this gap, we map LAMIN B1 occupancy across twelve human cell types encompassing pluripotent stem cells, intermediate progenitors, and differentiated cells from all three germ layers. Integrative analyses of this atlas with gene expression and repressive histone modification maps reveal that lamina-associated chromatin in all twelve cell types is organized into at least two subtypes defined by differences in LAMIN B1 occupancy, gene expression, chromatin accessibility, transposable elements, replication timing, and radial positioning. Imaging of fluorescently labeled DNA in single cells validates these subtypes and shows radial positioning of LADs with higher LAMIN B1 occupancy and heterochromatic histone modifications primarily embedded within the lamina. In contrast, the second subtype of lamina-associated chromatin is relatively gene dense, accessible, dynamic across development, and positioned adjacent to the lamina. Most genes gain or lose LAMIN B1 occupancy consistent with cell types along developmental trajectories; however, we also identify examples where the enhancer, but not the gene body and promoter, changes LAD state.
Altogether, this atlas represents the largest resource to date for peripheral chromatin organization studies and reveals an intermediate chromatin subtype.
A Saskatchewan multi-incident family was clinically characterized with Parkinson disease (PD) and Lewy body pathology. PD segregates as an autosomal-dominant trait, which could not be ascribed to any ...known mutation. DNA from three affected members was subjected to exome sequencing. Genome alignment, variant annotation and comparative analyses were used to identify shared coding mutations. Sanger sequencing was performed within the extended family and ethnically matched controls. Subsequent genotyping was performed in a multi-ethnic case-control series consisting of 2928 patients and 2676 control subjects from Canada, Norway, Taiwan, Tunisia, and the USA. A novel mutation in receptor-mediated endocytosis 8/RME-8 (DNAJC13 p.Asn855Ser) was found to segregate with disease. Screening of cases and controls identified four additional patients with the mutation, of which two had familial parkinsonism. All carriers shared an ancestral DNAJC13 p.Asn855Ser haplotype and claimed Dutch-German-Russian Mennonite heritage. DNAJC13 regulates the dynamics of clathrin coats on early endosomes. Cellular analysis shows that the mutation confers a toxic gain-of-function and impairs endosomal transport. DNAJC13 immunoreactivity was also noted within Lewy body inclusions. In late-onset disease which is most reminiscent of idiopathic PD subtle deficits in endosomal receptor-sorting/recycling are highlighted by the discovery of pathogenic mutations VPS35, LRRK2 and now DNAJC13. With this latest discovery, and from a neuronal perspective, a temporal and functional ecology is emerging that connects synaptic exo- and endocytosis, vesicular trafficking, endosomal recycling and the endo-lysosomal degradative pathway. Molecular deficits in these processes are genetically linked to the phenotypic spectrum of parkinsonism associated with Lewy body pathology.
IMPORTANCE: A unique pigmentary maculopathy was recently described in 6 patients with long-term exposure to pentosan polysulfate sodium (PPS), a long-standing oral therapy for interstitial cystitis. ...OBJECTIVE: To characterize the exposure characteristics and clinical manifestations of PPS–associated maculopathy. DESIGN, SETTING, AND PARTICIPANTS: In this multi-institutional case series, medical records of patients who exhibited the characteristic maculopathy in the setting of prior PPS exposure were retrospectively reviewed. Data were collected from August 1, 2012, to October 1, 2018, and data were analyzed from October 2018 to January 2019. MAIN OUTCOMES AND MEASURES: Drug exposure, visual acuity, and retinal imaging characteristics. RESULTS: Of the 35 included patients (70 eyes), 34 (97%) were female, and the median (range) age was 60 (37-79) years. The median (range) duration of PPS intake was 15 (3-22) years, and the median (range) cumulative exposure was 1.61 (0.44-4.31) kg. The leading visual symptoms were metamorphopsia, blurred vision, and prolonged dark adaptation. Median (range) logMAR visual acuity of all eyes was 0.10 (−0.12 to 1.18). Fundus examination often revealed hyperpigmented macular spots (34 of 64 eyes 53%) with interspersed pale-yellow deposits, although less commonly in eyes that exhibited retinal pigment epithelial atrophy (6 of 26 eyes 23%; P < .001). Optical coherence tomography showed foci of retinal pigment epithelium elevation or thickening associated with hyperreflectance on near-infrared reflectance imaging. Fundus autofluorescence imaging typically revealed a symmetric, confluent pattern of hyperautofluorescent and hypoautofluorescent spots that involved the fovea in all eyes and extended to the retinal periphery in 24 eyes (36%). Longitudinal evaluation demonstrated dynamic changes in pigmentary abnormalities. CONCLUSIONS AND RELEVANCE: These findings suggest that PPS–associated maculopathy is a vision-threatening condition that can manifest in the setting of long-term exposure to the drug. Multimodal imaging posits a distinctive clinical phenotype, characterized in this cohort by dynamic alterations within the retinal pigment epithelium and at the retinal pigment epithelium–photoreceptor interface. Ongoing work might explore causality and direct screening guidelines.
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